Silvia Rollefstad

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Carotid plaque characteristics and disease activity in rheumatoid arthritis.

Objective. Carotid plaques (CP) are predictive of acute coronary syndrome in patients with rheumatoid arthritis (RA), suggesting that atherosclerotic plaques in these patients are vulnerable. The objective of our study was to characterize vulnerability of CP in patients with RA compared to a control population, and between RA patients with different levels of disease activity. Methods. Ultrasound examination of carotid arteries was performed in 152 patients with RA and 89 controls. CP echolucency was evaluated by the Gray-Scale Median (GSM) technique. Lower GSM values indicate higher vulnerability of plaques. CP characteristics were compared between RA patients with active disease and in remission, and between patients and controls. All analyses were performed with adjustment for confounding factors (sex, age, smoking, and blood pressure). Poisson regression analysis was used for count data, mixed modeling for GSM and area per plaque, and analysis of covariance for minimum GSM value per patient. Results. Patients with RA more frequently had CP (median 2, range 0, 4) compared with controls (median 1, range 0, 3; p < 0.001), after adjustment for age and sex. Patients with active RA disease according to the Clinical Disease Activity Index (CDAI) had lower median GSM (p = 0.03), minimum GSM (p = 0.03), and a larger CP area (although the latter finding was not significant; p = 0.27), compared with patients with RA in remission. These findings were not confirmed for other disease measures (Simplified Disease Activity Index, Disease Activity Score-28, C-reactive protein, erythrocyte sedimentation rate). Conclusion. Patients with RA had more CP compared with controls and patients in CDAI remission, and controls had more stable CP than patients with active disease; these findings point to the importance of achieving remission in RA.

Treatment to lipid targets in patients with inflammatory joint diseases in a preventive cardio-rheuma clinic

Objectives To perform cardiovascular risk stratification in patients with inflammatory joint diseases (IJD) and treat to lipid targets according to recommendations. Methods We initiated a preventive cardio-rheuma clinic based on the unmet need of adequate cardiovascular prevention in IJD patients. A full cardiovascular risk stratification was performed at the first consultation (history of conventional risk factors and of cardiovascular disease, lipid measurement, blood pressure and ultrasound examination of both carotid arteries), and the patient was classified to either a primary or secondary cardiovascular prevention regime, or to have a low risk (no intervention). Lipid-lowering treatment was adjusted until at least two lipid targets were achieved. Results Of the 426 patients referred, 36.6% had a systematic coronary risk evaluation less than 5% (no lipid-lowering intervention). The remaining 270 patients ((rheumatoid arthritis (RA), n=165; ankylosing spondylitis (AS), n=70; and psoriatic arthritis (PsA), n=35) were assigned to either primary (n=63) or secondary prevention (n=207). There were significant differences between the patient groups regarding age (p<0.001), sex (p<0.001) and disease duration (p<0.001). Lipid changes in IJD patients were: total cholesterol −1.86±1.20 mmol/l (p<0.001); low-density lipoprotein cholesterol −1.74±1.11 (p<0.001); high-density lipoprotein cholesterol 0.01±0.30 (p=0.61); triglycerides −0.28±0.72 (p<0.001). The proportions of patients reaching at least two lipid targets were for RA 92.1%, AS 90.0% and PsA 82.9%. No serious adverse events were observed. Conclusions There was indication for cardiovascular prevention in a high proportion of IJD patients referred for cardiovascular risk stratification. Treatment to lipid targets was successful in approximately 90% of patients with IJD.

Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms

Objectives Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this study are to adapt the Systematic COronary Risk Evaluation (SCORE) algorithm with determinants of CVD risk in RA and to assess the accuracy of CVD risk prediction calculated with the adapted SCORE algorithm. Methods Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events. The SCORE algorithm was recalibrated by reweighing included traditional CVD risk factors and adapted by adding other potential predictors of CVD. Predictive performance of the recalibrated and adapted SCORE algorithms was assessed and the adapted SCORE was externally validated. Results Of the 1016 included patients with RA, 103 patients experienced a CVD event. Discriminatory ability was comparable across the original, recalibrated and adapted SCORE algorithms. The Hosmer–Lemeshow test results indicated that all three algorithms provided poor model fit (p<0.05) for the Nijmegen and external validation cohort. The adapted SCORE algorithm mainly improves CVD risk estimation in non-event cases and does not show a clear advantage in reclassifying patients with RA who develop CVD (event cases) into more appropriate risk groups. Conclusions This study demonstrates for the first time that adaptations of the SCORE algorithm do not provide sufficient improvement in risk prediction of future CVD in RA to serve as an appropriate alternative to the original SCORE. Risk assessment using the original SCORE algorithm may underestimate CVD risk in patients with RA.

Cardiovascular disease assessment in rheumatoid arthritis: a guide to translating knowledge of cardiovascular risk into clinical practice

As physicians we like to have evidence for making decisions about interventions to improve health. The evidence vacuum in the field of cardiovascular disease (CVD) prevention and clinical outcome in patients with rheumatoid arthritis (RA) has received vigorous attention in the recent literature. There is broad agreement that a patient with RA fulfilling the criteria established for the general population on CVD risk reduction should receive proven interventions, including smoking cessation, weight reduction, blood pressure control and lipid-lowering therapy. In accordance with these recommendations, and despite all the uncertainties about CVD treatment threshold, targets and outcome results in RA, we firmly advocate that CVD risk should be assessed and acted on in patients with RA as recommended for the general population, even while educational CVD-preventive programmes are being developed and hard CVD end point studies are undertaken in this patient population. The initial strategies for implementing CVD risk evaluation will necessarily be modest at first. There are several possible strategies for collection of data that can be incorporated into the daily routine during rheumatology consultations at outpatient clinics. We recommend starting with these simple procedures: 1. CVD risk factor recording and evaluation using risk calculators available for the general population 2. Referral of patients with high CVD risk to a primary care physician or a cardiologist skilled in this subject for follow-up 3. Providing information about excess CVD risk and how to modify it to the patients as major stakeholders

On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study

Objective To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. Methods Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. Results There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. Conclusions Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.

Rosuvastatin‐Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study

Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low‐density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA‐AS) study was to evaluate the effect of 18 months of intensive lipid‐lowering treatment with rosuvastatin with regard to change in carotid plaque height.

Hand, hip and knee osteoarthritis in a Norwegian population-based study - The MUST protocol

BackgroundKnowledge about the prevalence and consequences of osteoarthritis (OA) in the Norwegian population is limited. This study has been designed to gain a greater understanding of musculoskeletal pain in the general population with a focus on clinically and radiologically confirmed OA, as well as risk factors, consequences, and management of OA.Methods/DesignThe Musculoskeletal pain in Ullensaker STudy (MUST) has been designed as an observational study comprising a population-based postal survey and a comprehensive clinical examination of a sub-sample with self-reported OA (MUST OA cohort). All inhabitants in Ullensaker municipality, Norway, aged 40 to 79 years receive the initial population-based postal survey questionnaire with questions about life style, general health, musculoskeletal pain, self-reported OA, comorbidities, health care utilisation, medication use, and functional ability. Participants who self-report OA in their hip, knee and/or hand joints are asked to attend a comprehensive clinical examination at Diakonhjemmet Hospital, Oslo, including a comprehensive medical examination, performance-based functional tests, different imaging modalities, cardiovascular assessment, blood and urine samples, and a number of patient-reported questionnaires including five OA disease specific instruments. Data will be merged with six national data registries. A subsample of those who receive the questionnaire has previously participated in postal surveys conducted in 1990, 1994, and 2004 with data on musculoskeletal pain and functional ability in addition to demographic characteristics and a number of health related factors. This subsample constitutes a population based cohort with 20 years follow-up.DiscussionThis protocol describes the design of an observational population-based study that will involve the collection of data from a postal survey on musculoskeletal pain, and a comprehensive clinical examination on those with self-reported hand, hip and/or knee OA. These data, in addition to data from national registries, will provide unique insights into clinically and radiologically confirmed OA with respect to risk factors, consequences, and management.

Predictive Value of Arterial Stiffness and Subclinical Carotid Atherosclerosis for Cardiovascular Disease in Patients with Rheumatoid Arthritis

Objective. We evaluated the predictive value of these vascular biomarkers for cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA): aortic pulse wave velocity (aPWV), augmentation index (AIx), carotid intima-media thickness (cIMT), and carotid plaques (CP). They are often used as risk markers for CVD. Methods. In 2007, 138 patients with RA underwent clinical examination, laboratory tests, blood pressure testing, and vascular biomarker measurements. Occurrence of CVD events was recorded in 2013. Predictive values were assessed in Kaplan-Meier plots, log-rank, and crude and adjusted Cox proportional hazard (PH) regression analyses. Results. Baseline median age and disease duration was 59.0 years and 17.0 years, respectively, and 76.1% were women. CVD events occurred in 10 patients (7.2%) during a mean followup of 5.4 years. Compared with patients with low aPWV, AIx, cIMT, and without CP, patients with high aPWV (p < 0.001), high AIx (p = 0.04), high cIMT (p = 0.01), and CP (p < 0.005) at baseline experienced more CVD events. In crude Cox PH regression analyses, aPWV (p < 0.001), cIMT (p < 0.001), age (p = 0.01), statin (p = 0.01), and corticosteroid use (p = 0.01) were predictive of CVD events, while AIx was nonsignificant (p = 0.19). The Cox PH regression estimates for vascular biomarkers were not significantly altered when adjusting individually for demographic variables, traditional CVD risk factors, RA disease-related variables, or medication. All patients who developed CVD had CP at baseline. Conclusion. CP, aPWV, and cIMT were predictive of CVD events in this cohort of patients with RA. Future studies are warranted to examine the additive value of arterial stiffness and carotid atherosclerosis markers in CVD risk algorithms. Regional Ethical Committee approval numbers 2009/1582 and 2009/1583.

EULAR Task Force Recommendations on Annual Cardiovascular Risk Assessment for Patients with Rheumatoid Arthritis: An Audit of the Success of Implementation in a Rheumatology Outpatient Clinic

Objective. EULAR recommendations for cardiovascular disease (CVD) risk management include annual CVD risk assessments for patients with rheumatoid arthritis (RA). We evaluated the recording of CVD risk factors (CVD-RF) in a rheumatology outpatient clinic, where EULAR recommendations had been implemented. Further, we compared CVD-RF recordings between a regular rheumatology outpatient clinic (RegROC) and a structured arthritis clinic (AC). Methods. In 2012, 1142 RA patients visited the rheumatology outpatient clinic: 612 attended RegROC and 530 attended AC. We conducted a search in the patient journals to ascertain the rate of CVD-RF recording. Results. The overall CVD-RF recording rate was 40.1% in the rheumatology outpatient clinic, reflecting a recording rate of 59.1% in the AC and 23.6% in the RegROC. The odds ratios for having CVD-RFs recorded for patients attending AC compared to RegROC were as follows: blood pressure: 12.4, lipids: 5.0-6.0, glucose: 9.1, HbA1c: 6.1, smoking: 1.4, and for having all the CVD-RFs needed to calculate the CVD risk by the systematic coronary risk evaluation (SCORE): 21.0. Conclusion. The CVD-RF recording rate was low in a rheumatology outpatient clinic. However, a systematic team-based model was superior compared to a RegROC. Further measures are warranted to improve CVD-RF recording in RA patients.